Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that appears in the large intestine or colon with periods of exacerbated symptoms and periods that are relatively symptom free. UC patients often experience the same symptoms as irritable bowel syndrome (IBS) patients, which is a much less serious condition, making a definitive diagnosis much more complicated. Similarly, patients with indeterminate colitis may have a form of colitis that is different from UC, and more similar to Crohn's colitis, another related form of intestinal IBD.
Symptoms of UC are anatomically heterogeneous in their presentation between patients. UC patients for example can present with disease in a range of extent from the recto-sigmoid only on to degrees of involvement including the entire colon. Initially, patients treated medically may be started on non-specific anti-inflammatory medications, most commonly mesalamine (5-ASA). Non-responders to a trial of medications may then be escalated in their therapy with cytotoxic or biologic medications. This “step-up” approach typically using mesalamine to treat active UC, is associated with clinical treatment failures in 60% of patients with moderate UC, compared to 80% treated with placebo. Moreover, a clinical response favoring doses of mesalamine greater than 2.5 grams per day has not been clearly shown despite clinical practice to the contrary.
Since biologics are associated with significantly increased costs compared to oral anti-inflammatory drugs, the early identification of patients who do not respond to mesalamine or conversely, who would respond to other therapies is important. The “step-up” medication strategy currently used does not take gender difference into consideration nor the locations of the disease within the colon. The same drug intervention strategy is applied to almost all UC patients, which is believed to be one of the key factors responsible for the high clinical treatment failure.
Numerous systems have been developed for inflammatory bowel disease (IBD) biomarkers including the use of fecal calprotectin and lactoferrin proteins for identifying patients with inflammatory bowel disease (IBD), assessing disease severity and for predicting relapses; the use of serum anti-Saccharomyces cerevisiae antibody (ASCA) and perinuclear antoneutriphil cytoplasmic antibody (pANCA) biomarkers to differentiate Crohn's Disease (CD) from UC; and the use of serum anti-OmpC IgA anti-CBir1 biomarkers with ASCA and other biomarker assays for IBD diagnosis as well as UC and CD differentiation. IBD disease biomarkers including anti-GM-CSF antibody, CD11b, TNF-a, CRP, aldo-keto reductase family 1 B10 (AKR1B10), perforin, NF-kB, CXC-chemokines, aquaporins, kinesins, adaptor protein-1 (AP-1), C5a, IL-2R, integrins, HCC-4, IL-7, MCP-1, MSP protein, IL-11, G-CSF, adrenoreceptors, ST2, E-cadhein, KC, IL-12/23p40, IL-17, chlorotyrosine, PAP/REG3, MIF, DMBT1, LCN2, IL-22, haptoglobin, CCL20, IL-6, IL-33, CAP37, E4A (UBE4A), CXCL16, resistin, apolipoprotein A-IV, beta-defensin, NOD2/CARD15, NOD1/CARD4, toll-like receptors (TLR) 2 and 4, leptin, adiponectin, IL-10, DPP-IV, and CXCR4 have also been identified. Such biomarkers have been used for determining the responsiveness of steroid and biological treatments. However, until now, there have been no method or system developed for determining the responsiveness of a patient to mesalamine for the treatment of active UC.
As previously stated, one of the first lines of conventional UC clinical treatment is the use of mesalamine (5-ASA). However, the efficacy of mesalamine in active UC is only about 30-40%. UC pathophysiology and factors that influence the response to mesalamine treatment are not well known. The identified significant differences in protein profiling from different genders and anatomic colitis locations demonstrate that UC is a complicated disease. Accordingly, a need exist for a process and system for predicting the potential efficacy of a patient's response to mesalamine suffering from UC. It is also desirable to have a process and a system for developing an effective strategy for treatment of patients suffering from UC and a new, safe, effective, and potentially gender and colitis location dependent therapeutics.